This proposal is for an ancillary study to and approved by the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) in response to PAR-09-247. The broad, long-term objective is to improve the health of people with Non-Alcoholic Fatty Liver Disease (NAFLD). The immediate objective is to overcome a key barrier in the diagnosis and assessment of NAFLD: the lack of accurate non-invasive biomarkers to differentiate NASH - the more rapidly progressive variant and target for therapeutic intervention - from isolated steatosis, evaluate NAFLD disease activity, and stage fibrosis. Health relatedness: NAFLD is the most common chronic liver disease in children and adults in the United States, and it is intimately related to insulin resistance and obesity. The condition may progress to cirrhosis and liver cancer, and it contributes to the development of diabetes and cardiovascular disease. Currently, accurate assessment of NAFLD requires liver biopsy, a requirement that hampers clinical care and impedes NAFLD research. This proposal will develop much-needed non-invasive MR biomarker panels to evaluate NAFLD. The integration of these biomarker panels into clinical practice and clinical trial endpoints will advance NAFLD care and research. The specific aims are to develop panels of MR biomarkers in children and adults with NAFLD to diagnose the presence of NASH (Aim 1), grade NAFLD disease activity (Aim 2), and diagnose the presence of moderate (Aim 3a) or advanced (Aim 3b) fibrosis. The reference standard will be centrally scored liver histology. Design: We propose a five-site, prospective, observational, cross-sectional ancillary study to the NASH CRN, the leading NAFLD research network in the United States. The NASH CRN will provide a large, ethnically diverse population of clinically and histologically characterized subjects. Methods: 150 children and 150 adults in the NASH CRN with liver biopsy-confirmed NAFLD will be enrolled and have research MR examinations within 60 days of biopsy. MR examinations will include advanced MR imaging, MR spectroscopy, and MR elastography techniques and last 45-60 minutes without contrast agent use. Techniques will be optimized to mitigate confounding effects. Candidate MR biomarkers will be measured including fat fraction, transverse relaxation values, shear stiffness, true diffusion coefficient, perfusion fraction, and extrahepatic adipose tissue volumes. Statistical analyses: MR measurements will be compared with histology findings. Multivariate models will be built to develop pediatric- and adult-specific MR biomarker panels to diagnose the presence of NASH, grade NAFLD disease activity, and diagnose moderate and advanced fibrosis. The development of accurate, precise non-invasive MR biomarker panels to evaluate NAFLD will advance both clinical care and clinical research.